To investigate the role of high mobility group protein B1 (HMGB1) inhibitor in regulating cardiac allograft rejection in mice and its molecular mechanism.

Heart transplantation model was established by using 20 C57 mice as recipients and 20 BALB/c mice as donors, which were randomly divided into model group and observation group. The mice in the observation group were intraperitoneally injected with HMGB1 inhibitor ammonium glycyrrhizinate 50 mg/kg, and the mice in the model group were intraperitoneally injected with normal saline of the same volume. After transplantation, mice in each group were given drugs until the transplanted heart stopped beating. The survival time of transplanted heart was observed in two groups. The cardiac pathological score was analyzed by hematoxylin and eosin (HE) staining. Interleukin (IL)-1β and tumor necrosis factor-α (TNF-α) in peripheral serum of mice in two groups were analyzed by enzyme linked immunosorbent assay (ELISA). The angiopathy of transplanted heart was analyzed by EVG staining. The percentage of macrophages was analyzed by flow cytometry. The apoptosis level of myocardial cells was analyzed by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining. T-test was used to compare the data between groups.

The survival time of donor heart in the observation group [(7.60±2.12) d] was significantly longer than that in the model group [(15.90±3.03) d, t=7.091, P<0.05]. The pathological score of donor heart in the observation group (1.80±0.79) was significantly higher than that in the model group (4.10±0.74, t=6.734, P<0.05). Serum inflammatory factor IL-1β and TNF-α of mice in observation group [(59.89±18.98), (56.51±10.89) pg/ml] was significantly lower than [(106.99±14.97), (101.11±11.44) pg/ml, t=8.532, 8.931, P<0.05). The donor heart parenchymal response score and graft arterial disease score in the observation group (2.20±0.63, 1.70±0.67) was significantly lower than that in the model group (3.60±0.52, 3.30±0.67, t=5.422, 5.301, P<0.05). The proportion of macrophage infiltration in the donor heart of mice in the observation group [(16.67±2.49)%] was significantly lower than that of mice in the model group [(34.43±4.59)%, t=10.750, P<0.05]. The percentage of apoptosis of donor heart cells in the observation group [(20.68±3.01)%] was significantly lower than that in the model group [(44.19±3.78)%, t=15.370, P<0.05].

HMGB1 inhibitor ammonium glycyrrhizinate can significantly inhibit the infiltration of inflammatory cells and the release of inflammatory factors, reduce cardiomyocyte apoptosis, and thus prolong the survival time of heart transplantation.

High mobility group protein B1; Heart transplant; Inflammatory reaction; Apoptosis